Search For Quantitative Trait Loci Research Articles

Inheritance of genomic regions and genes associated with number of oocytes and embryos in Gir cattle through daughter design

Over the past decades, daughter designs, including genotyped sires and their genotyped daughters, have been used as an approach to identify quantitative trait loci (QTL) related with economic traits. The aim of this study was to identify genomic regions inherited by Gir sire families and genes associated with number of viable oocytes (VO), total number of oocytes (TO) and number of embryos (EMBR) based on a daughter design approach. In total, 15 Gir sire families were selected. The number of daughters per family ranged from 26 to 395, which were genotyped with different SNP panels and imputed to the Illumina BovineHD BeadChip (777K) and had phenotypes for oocyte and embryo production. Daughters had phenotypic data for VO, TO, and EMBR. The search for QTL was performed through Genome-Wide Association Study (GWAS) based on genomic best linear unbiased prediction (gBLUP). QTL were found for each trait among and within families based on the top 10 genomic windows with the greatest genetic variance. For EMBR, genomic windows identified among families were located on BTA4, BTA5, BTA6, BTA7, BTA8, BTA13, BTA16 and BTA17, and they were most frequent on BTA7 within families. For VO, genomic windows were located on BTA2, BTA4, BTA5, BTA7, BTA17, BTA21, BTA22, BTA23 and BTA27 among families, being most frequent on BTA8 within families. For TO, top 10 genomic windows were identified on BTA2, BTA4, BTA5, BTA7, BTA17, BTA21, BTA22, BTA26 and BTA27, being most frequent on BTA7 and BTA8 within families. Considering all results, the greatest number of genomic windows was found on BTA7, where VCAN, XRCC4, TRNAC-ACA, HAPLN1 and EDIL3 genes were identified in the common regions. In conclusion, 15 Gir sire families with 26 to 395 daughters per family with phenotypes for oocyte and embryo production helped to identify the inheritance of several genomic regions, especially on BTA7, where EDIL3, HAPLN1 and VCAN candidate genes were associated with number of oocytes and embryos in Gir cattle families.

Mapping of a major QTL for increased robustness and detection of genome assembly errors in Asian seabass (Lates calcarifer)

BackgroundFor Asian seabass (Lates calcarifer, Bloch 1790) cultured at sea cages various aquatic pathogens, complex environmental and stress factors are considered as leading causes of disease, causing tens of millions of dollars of annual economic losses. Over the years, we conducted farm-based challenges by exposing Asian seabass juveniles to complex natural environmental conditions. In one of these challenges, we collected a total of 1,250 fish classified as either ‘sensitive’ or ‘robust’ individuals during the 28-day observation period.ResultsWe constructed a high-resolution linkage map with 3,089 SNPs for Asian seabass using the double digest Restriction-site Associated DNA (ddRAD) technology and a performed a search for Quantitative Trait Loci (QTL) associated with robustness. The search detected a major genome-wide significant QTL for increased robustness in pathogen-infected marine environment on linkage group 11 (ASB_LG11; 88.9 cM to 93.6 cM) with phenotypic variation explained of 81.0%. The QTL was positioned within a > 800 kb genomic region located at the tip of chromosome ASB_LG11 with two Single Nucleotide Polymorphism markers, R1-38468 and R1-61252, located near to the two ends of the QTL. When the R1-61252 marker was validated experimentally in a different mass cross population, it showed a statistically significant association with increased robustness. The majority of thirty-six potential candidate genes located within the QTL have known functions related to innate immunity, stress response or disease. By utilizing this ddRAD-based map, we detected five mis-assemblies corresponding to four chromosomes, namely ASB_LG8, ASB_LG9, ASB_LG15 and ASB_LG20, in the current Asian seabass reference genome assembly.ConclusionAccording to our knowledge, the QTL associated with increased robustness is the first such finding from a tropical fish species. Depending on further validation in other stocks and populations, it might be potentially useful for selecting robust Asian seabass lines in selection programs.

X-linked genes influence various complex traits in dairy cattle

BackgroundThe search for quantitative trait loci (QTL) affecting traits of interest in mammals is frequently limited to autosomes, with the X chromosome excluded because of its hemizygosity in males. This study aimed to assess the importance of the X chromosome in the genetic determinism of 11 complex traits related to milk production, milk composition, mastitis resistance, fertility, and stature in 236,496 cows from three major French dairy breeds (Holstein, Montbéliarde, and Normande) and three breeds of regional importance (Abondance, Tarentaise, and Vosgienne).ResultsEstimates of the proportions of heritability due to autosomes and X chromosome (h²X) were consistent among breeds. On average over the 11 traits, h²X=0.008 and the X chromosome explained ~ 3.5% of total genetic variance. GWAS was performed within-breed at the sequence level (~ 200,000 genetic variants) and then combined in a meta-analysis. QTL were identified for most breeds and traits analyzed, with the exception of Tarentaise and Vosgienne and two fertility traits. Overall, 3, 74, 59, and 71 QTL were identified in Abondance, Montbéliarde, Normande, and Holstein, respectively, and most were associated with the most-heritable traits (milk traits and stature). The meta-analyses, which assessed a total of 157 QTL for the different traits, highlighted new QTL and refined the positions of some QTL found in the within-breed analyses. Altogether, our analyses identified a number of functional candidate genes, with the most notable being GPC3, MBNL3, HS6ST2, and DMD for dairy traits; TMEM164, ACSL4, ENOX2, HTR2C, AMOT, and IRAK1 for udder health; MAMLD1 and COL4A6 for fertility; and NRK, ESX1, GPR50, GPC3, and GPC4 for stature.ConclusionsThis study demonstrates the importance of the X chromosome in the genetic determinism of complex traits in dairy cattle and highlights new functional candidate genes and variants for these traits. These results could potentially be extended to other species as many X-linked genes are shared among mammals.

Modeling allelic diversity of multiparent mapping populations affects detection of quantitative trait loci.

The search for quantitative trait loci that explain complex traits such as yield and drought tolerance has been ongoing in all crops. Methods such as biparental quantitative trait loci mapping and genome-wide association studies each have their own advantages and limitations. Multiparent advanced generation intercross populations contain more recombination events and genetic diversity than biparental mapping populations and are better able to estimate effect sizes of rare alleles than association mapping populations. Here, we discuss the results of using a multiparent advanced generation intercross population of doubled haploid maize lines created from 16 diverse founders to perform quantitative trait loci mapping. We compare 3 models that assume bi-allelic, founder, and ancestral haplotype allelic states for quantitative trait loci. The 3 methods have differing power to detect quantitative trait loci for a variety of agronomic traits. Although the founder approach finds the most quantitative trait loci, all methods are able to find unique quantitative trait loci, suggesting that each model has advantages for traits with different genetic architectures. A closer look at a well-characterized flowering time quantitative trait loci, qDTA8, which contains vgt1, highlights the strengths and weaknesses of each method and suggests a potential epistatic interaction. Overall, our results reinforce the importance of considering different approaches to analyzing genotypic datasets, and shows the limitations of binary SNP data for identifying multiallelic quantitative trait loci.

Genome-wide characterization of human minisatellite VNTRs: population-specific alleles and gene expression differences.

Variable Number Tandem Repeats (VNTRs) are tandem repeat (TR) loci that vary in copy number across a population. Using our program, VNTRseek, we analyzed human whole genome sequencing datasets from 2770 individuals in order to detect minisatellite VNTRs, i.e., those with pattern sizes ≥7 bp. We detected 35 638 VNTR loci and classified 5676 as commonly polymorphic (i.e. with non-reference alleles occurring in >5% of the population). Commonly polymorphic VNTR loci were found to be enriched in genomic regions with regulatory function, i.e. transcription start sites and enhancers. Investigation of the commonly polymorphic VNTRs in the context of population ancestry revealed that 1096 loci contained population-specific alleles and that those could be used to classify individuals into super-populations with near-perfect accuracy. Search for quantitative trait loci (eQTLs), among the VNTRs proximal to genes, indicated that in 187 genes expression differences correlated with VNTR genotype. We validated our predictions in several ways, including experimentally, through the identification of predicted alleles in long reads, and by comparisons showing consistency between sequencing platforms. This study is the most comprehensive analysis of minisatellite VNTRs in the human population to date.

Influence of quantitative trait loci on growth traits of chromosome 1 in Sanjabi lambs during the first year of growth

Abstract This study aimed to detect the quantitative trait loci (QTL) which affecting the growth traits in some parts of chromosomes 1 of Sanjabi lambs. The study population consisted of six groups of fathers which had an average of 39.17 lambs. Initially, the fathers were genotyped for eight microsatellite markers on chromosome 1, and the offspring of the heterozygote fathers were genotyped. The quantitative traits were the body’s weight at birth, 3, 6, 9, and 12 months, which were corrected for the fixed effects of year of birth, sex, and birth type. QTL search was performed by interval mapping based on a regression model for each cM (Centimorgan) of the chromosomes. In total, one QTL in the 235 cM of chromosome 1 was identified from the beginning of the chromosome in associate with weaning weight. The sire substitution effect for both families was 2.14 kg. The confidence interval estimation of the detected QTL that was estimated using the Bootstrap method was 225–238 cM of chromosome 1. This QTL was determined between the MCM137 and MCM130 markers and at a distance of about 9 cM from the MCM137 marker. If this QTL was approved in the next research, it can be used in Marker-assisted selection programs. In this case, more accuracy should be achieved for the evaluation of superior animals.

Short communication: The genotype of growth hormone gene that affects the birth weight and average daily gain in crossbred beef cattle

Abstract. Hartatik T., Fathoni A, Bintara S., Ismaya, Panjono, Widyobroto B.P, Agus A, Budisatria I.G.S, Leroy P. 2020. Short communication: The genotype of growth hormone gene that affects the birth weight and average daily gain in crossbred beef cattle. Biodiversitas 21: 941-945. Growth Hormone gene has been proposed to direct search for quantitative trait loci, and polymorphisms at these loci have been associated with several production traits in bovine. This research aimed to investigate the association of the genotype of partial growth hormone gene with birth weight and average daily gain in crossbred beef cattle. The materials of this research consist of 47 samples from four different breeds. Birth weight was measured just after calving delivery from the mother. The average daily gain was calculated from the period since birth weight to the second weight (90 days). Genotyping of the growth hormone gene was determined by the sequencing and PCR-RFLP method with the AluI restriction enzyme. The association between genotype and growth traits data was analyzed using analysis of variance (ANOVA) by RStudio version 1.1.383. The results showed the significantly different (P<0.001) in birth weight and average daily gain according to the different breed. Friesian Holstein breed showed the highest birth weight, followed by Belgian Blue Bull cross and others. The genotype valine/valine only occurs in Belgian blue bull cross and Wagyu bull cross cattle and showed moderate birth weight. Genotype affects birth weight significantly (P<0.001). The birth weight for genotype leucine/leucine, leucine/valine, and valine/valine was 34.82±18.13, 25.31±13.10, and 29.35±13.65, respectively. There was no significant difference in average daily genes according to the different genotypes. In conclusion, the growth hormone gene was probably one of the molecular genetics markers for excellent growth traits in different crossbred beef cattle.

PSX-14 Recent advances in understanding genetic variants associated with growth, carcass and meat productivity traits in sheep (Ovis aries): an update

Abstract Identification of quantitative trait loci (QTL) and candidate genes that affect growth intensity is a prerequisite for the marker-assisted selection for economically important traits. The number of QTL studies on sheep is relatively small in comparison to those on cattle and pigs. Current QTL Sheep database (Sheep QTLdb) contains information on 1658 QTL for 225 different traits. A few genes and markers associated with growth, carcass and meat productivity traits have been reported. The information about QTLs from the Sheep QTLdb cannot be directly used in marker assisted selection due to the lack of essential information such as effective and reference alleles, the effect direction, etc., and requires manual curation and validation. In this study we performed comprehensive search for QTLs focusing on single nucleotide polymorphisms (SNPs) associated with growth and meat traits in sheep. Using 15 different keywords combinations we found 152 papers (including duplicates). Next, all the found papers were manually curated by two researches and filtered by the relevance. We selected the most relevant papers that led to the final list of 17 publications. From these 17 papers we extracted information about associated genes and QTLs (SNPs). We extracted information about associated SNPs with all available information (effect sizes, effective and reference alleles etc). In total we found information about 156 SNP-trait associations (123 unique SNPs). Also we made the list of 164 unique genes associated with growth, carcass and meat productivity traits. As the result we made the database which contains information about 156 SNP-trait associations (123 unique SNPs) and list of 165 associated genes. The updated information is freely available at https://github.com/Defrag1236/Ovines_2018. This information can be useful for further association studies and preliminary estimation of genetic variability for economically important traits in different breeds.

Recent advances in understanding genetic variants associated with growth, carcass and meat productivity traits in sheep (Ovis aries): an update.

Identification of quantitative trait loci (QTLs) and candidate genes that affect growth intensity is a prerequisite for the marker-assisted selection of economically important traits. The number of QTL studies on sheep is relatively small in comparison to those on cattle and pigs. The current QTL sheep database – Sheep QTLdb – contains information on 1658 QTLs for 225 different traits. A few genes and markers associated with growth, carcass and meat productivity traits have been reported. The information about QTLs from the Sheep QTLdb cannot be directly used in marker-assisted selection due to the lack of essential information such as effective and reference alleles, the effect direction etc., and it requires manual curation and validation. In this study we performed a comprehensive search for QTLs focusing on single nucleotide polymorphisms (SNPs) associated with growth and meat traits in sheep. The database contains information about 156 SNP–trait associations (123 unique SNPs) and a list of 165 associated genes. The updated information is freely available at https://github.com/Defrag1236/Ovines_2018 (last access: 18 September 2019). This information can be useful for further association studies and preliminary estimation of genetic variability for economically important traits in different breeds.

Development of microsatellite markers using next-generation sequencing for the fish Colossoma macropomum.

Tambaqui (Colossoma macropomum) is a fish species from the Amazon and Orinoco Rivers, with favorable characteristics to the cultivation system and great market acceptance in South America. However, the construction of a genetic map for the genetic improvement of this species is limited by the low number of molecular markers currently described. Thus, this study aimed to validate gene-associated and anonymous (non-genic) microsatellites obtained by next generation sequencing (RNA-seq and whole genome shotgun-WGS, respectively), for future construction of a genetic map and search for quantitative trait loci (QTL) in this species. In the RNA-seq data, the observed and expected heterozygosity (Ho and He) ranged from 0.09 to 0.73, and 0.09 to 0.85, respectively. In the WGS data, Ho and He ranged from 0.33 to 0.95, and 0.28 to 0.92, respectively. In general, the evaluation of 200 markers resulted in 45 polymorphic loci, of which 14 were gene-associated (RNA-Seq) and 31 were anonymous (WGS). Moreover, some markers were related to genes of the immune system, biological regulation/control and biogenesis. This study contributes to increase the number of molecular markers available for genetic studies in C. macropomum, which will allow the development of breeding programs assisted by molecular markers.

Detection of QTL for greasy fleece weight in sheep using a 50K single nucleotide polymorphism chip.

Genome-wide association studies (GWAS) have introduced an influential tool in the search for quantitative trait loci (QTL) influencing economically important traits in sheep. To identify QTL associated with greasy fleece weight, a GWAS with 50K single nucleotide polymorphisms (SNPs) was performed in a Baluchi sheep population. Association with greasy fleece weights was tested using the software Plink. The results of our GWAS provided three novel SNP markers and candidate genes associated with greasy fleece weight. A total of three chromosome-wide significant associations were detected for SNP on chromosomes 17 and 20 affecting greasy fleece weight across the four shearing. One of the significant SNP markers was located within ovine known genes namely FAM101A. Further investigation of these identified regions in validation studies will facilitate the identification of strong candidate genes for wool production in sheep.

Genetic polymorphisms and their association with brain and behavioural measures in heterogeneous stock mice

Although the search for quantitative trait loci for behaviour remains a considerable challenge, the complicated genetic architecture of quantitative traits is beginning to be understood. The current project utilised heterogeneous stock (HS) male mice (n = 580) to investigate the genetic basis for brain weights, activity, anxiety and cognitive phenotypes. We identified 126 single nucleotide polymorphisms (SNPs) in genes involved in regulation of neurotransmitter systems, nerve growth/death and gene expression, and subsequently investigated their associations with changes in behaviour and/or brain weights in our sample. We found significant associations between four SNP-phenotype pairs, after controlling for multiple testing. Specificity protein 2 (Sp2, rs3708840), tryptophan hydroxylase 1 (Tph1, rs262731280) and serotonin receptor 3A (Htr3a, rs50670893) were associated with activity/anxiety behaviours, and microtubule-associated protein 2 (Map2, rs13475902) was associated with cognitive performance. All these genes except for Tph1 were expressed in the brain above the array median, and remained significantly associated with relevant behaviours after controlling for the family structure. Additionally, we found evidence for a correlation between Htr3a expression and activity. We discuss our findings in the light of the advantages and limitations of currently available mouse genetic tools, suggesting further directions for association studies in rodents.

Consomic mouse strain selection based on effect size measurement, statistical significance testing and integrated behavioral z-scoring: focus on anxiety-related behavior and locomotion.

BackgroundSelecting chromosome substitution strains (CSSs, also called consomic strains/lines) used in the search for quantitative trait loci (QTLs) consistently requires the identification of the respective phenotypic trait of interest and is simply based on a significant difference between a consomic and host strain. However, statistical significance as represented by P values does not necessarily predicate practical importance. We therefore propose a method that pays attention to both the statistical significance and the actual size of the observed effect. The present paper extends on this approach and describes in more detail the use of effect size measures (Cohen’s d, partial eta squared - ηp2) together with the P value as statistical selection parameters for the chromosomal assignment of QTLs influencing anxiety-related behavior and locomotion in laboratory mice.ResultsThe effect size measures were based on integrated behavioral z-scoring and were calculated in three experiments: (A) a complete consomic male mouse panel with A/J as the donor strain and C57BL/6J as the host strain. This panel, including host and donor strains, was analyzed in the modified Hole Board (mHB). The consomic line with chromosome 19 from A/J (CSS-19A) was selected since it showed increased anxiety-related behavior, but similar locomotion compared to its host. (B) Following experiment A, female CSS-19A mice were compared with their C57BL/6J counterparts; however no significant differences and effect sizes close to zero were found. (C) A different consomic mouse strain (CSS-19PWD), with chromosome 19 from PWD/PhJ transferred on the genetic background of C57BL/6J, was compared with its host strain. Here, in contrast with CSS-19A, there was a decreased overall anxiety in CSS-19PWD compared to C57BL/6J males, but not locomotion.ConclusionsThis new method shows an improved way to identify CSSs for QTL analysis for anxiety-related behavior using a combination of statistical significance testing and effect sizes. In addition, an intercross between CSS-19A and CSS-19PWD may be of interest for future studies on the genetic background of anxiety-related behavior.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0411-4) contains supplementary material, which is available to authorized users.

Detection of Growth-Related Quantitative Trait Loci and High-Resolution Genetic Linkage Maps Using Simple Sequence Repeat Markers in the Kelp Grouper (Epinephelus bruneus).

To initiate breeding programs for kelp grouper (Epinephelus bruneus), the establishment of genetic linkage maps becomes essential accompanied by the search for quantitative trait loci (QTLs) that may be utilized in selection programs. We constructed a high-resolution genetic linkage map using 1055 simple sequence repeat (SSR) markers in an F1 family. Genome-wide and chromosome-wide significances of growth-related QTLs (body weight: BW and total length: TL) were detected using non-parametric mapping, Kruskal-Wallis analysis, simple interval mapping (IM), and a permutation test (PT). Two stages and two families of fish were used to confirm the QTL regions. Ultimately, 714 SSR markers were matched that evenly covered the 24 linkage groups. In total, 509 and 512 markers were localized to the female and male maps, respectively. The genome lengths were approximately 1475.95 and 1370.39cM and covered 84.68 and 83.21% of the genome, with an average interval of 4.1 and 4.0cM, in females and males, respectively. One major QTL affecting BW and TL was found on linkage group EBR 17F that identified for 1% of the genome-wide significance and accounted for 14.6-18.9% and 14.7-18.5% of the phenotypic variance, and several putative QTL with 5% chromosome-wide significance were detected on eight linkage groups. Furthermore, the confirmed results of the regions harboring the major and putative QTLs showed consistent significant experiment-wide values of 1 and 5% as well as a chromosome-wide value of 5%. We identified growth-related QTLs that could be applied to find candidate genes for growth traits in further studies and potentially useful in marker assisted selection (MAS) breeding.

Detection of Growth-Related Quantitative Trait Loci and High-Resolution Genetic Linkage Maps Using Simple Sequence Repeat Markers in the Kelp Grouper (Epinephelus bruneus).

To initiate breeding programs for kelp grouper (Epinephelus bruneus), the establishment of genetic linkage maps becomes essential accompanied by the search for quantitative trait loci that may be utilized in selection programs. We constructed a high-resolution genetic linkage map using 1055 simple sequence repeat (SSR) markers in an F1 family. Genome-wide and chromosome-wide significances of growth-related quantitative trait loci (QTLs) (body weight (BW) and total length (TL)) were detected using non-parametric mapping, Kruskal-Wallis (K-W) analysis, simple interval mapping (IM) and a permutation test (PT). Two stages and two families of fish were used to confirm the QTL regions. Ultimately, 714 SSR markers were matched that evenly covered the 24 linkage groups. In total, 509 and 512 markers were localized to the female and male maps, respectively. The genome lengths were approximately 1475.95 and 1370.39 cM and covered 84.68 and 83.21 % of the genome, with an average interval of 4.1 and 4.0 cM, in females and males, respectively. One major QTL affecting BW and TL was found on linkage group EBR 17F that identified for 1 % of the genome-wide significance and accounted for 14.6–18.9 and 14.7–18.5 % of the phenotypic variance, and several putative QTL with 5 % chromosome-wide significance were detected on eight linkage groups. Furthermore, the confirmed results of the regions harboring the major and putative QTLs showed consistent significant experiment-wide values of 1 and 5 % as well as a chromosome-wide value of 5 %. We identified growth-related QTLs that could be applied to find candidate genes for growth traits in further studies, and potentially useful in MAS breeding.Electronic supplementary materialThe online version of this article (doi:10.1007/s10126-015-9673-5) contains supplementary material, which is available to authorized users.

Polymorphism of the Insulin-like growth factor 1 receptor gene (IGF1R/e10/MspI and IGF1R/e16/RsaI) in four dairy breeds and its association with milk traits

Studying candidate genes for significant economic traits could be directly applied in a search for quantitative trait loci. There is growing evidence that the IGF-I/IGF-1R signaling pathway can be involved in mammary gland development and milk synthesis control. The bovine Insulin-like growth factor 1 receptor gene encodes a transmembrane ligand-activated tyrosine protein kinase. The presence of two synonymous mutations (IGF1R/e10/MspI and IGF1R/e16/RsaI) have been validated in 4 dairy breeds (Polish Holstein-Friesian, Holstein-Friesian, Montbeliarde and Jersey). A total of 1167 blood samples were genotyped. Five milk performance traits, i.e., milk yield (MY), fat yield (FY), protein yield (PY), fat percentage (F%), and protein percentage (P%) were used in the association analysis. The data for the full 305-day milk production (1st, 2nd and 3rd lactation, collected between 2007 and 2014) were obtained from the official farm records. The TT genotype of both polymorphisms was found to be associated with the highest yields (milk yield – MY, fat yield – FY and protein yield – PY), while the lowest values were recorded for the CC genotype (P≤0.01). In order to confirm or refute the association found, statistical analysis of the combined genotypes was also performed. Irrespective of breed and lactation order, cows with the TT/TT genotype combination were usually characterized by the highest milk, fat and protein yields, as opposed to the least favorable CC/CC combination. As regards the milk yield, the differences were in the range of 2000kg (MO) to 3000kg per lactation (PHF, HF) (P≤0.01). Significant differences at the level of 80÷130kg for FY and 50÷100kg for PY were also recorded (P≤0.01). No statistical differences in fat and protein content were found. In light of these results, the IGF1R gene can be proposed as a candidate gene for milk traits in cattle.

Using whole-genome sequences of the LG/J and SM/J inbred mouse strains to prioritize quantitative trait genes and nucleotides.

BackgroundThe laboratory mouse is the most commonly used model for studying variation in complex traits relevant to human disease. Here we present the whole-genome sequences of two inbred strains, LG/J and SM/J, which are frequently used to study variation in complex traits as diverse as aging, bone-growth, adiposity, maternal behavior, and methamphetamine sensitivity.ResultsWe identified small nucleotide variants (SNVs) and structural variants (SVs) in the LG/J and SM/J strains relative to the reference genome and discovered novel variants in these two strains by comparing their sequences to other mouse genomes. We find that 39% of the LG/J and SM/J genomes are identical-by-descent (IBD). We characterized amino-acid changing mutations using three algorithms: LRT, PolyPhen-2 and SIFT. We also identified polymorphisms between LG/J and SM/J that fall in regulatory regions and highly informative transcription factor binding sites (TFBS). We intersected these functional predictions with quantitative trait loci (QTL) mapped in advanced intercrosses of these two strains. We find that QTL are both over-represented in non-IBD regions and highly enriched for variants predicted to have a functional impact. Variants in QTL associated with metabolic (231 QTL identified in an F16 generation) and developmental (41 QTL identified in an F34 generation) traits were interrogated and we highlight candidate quantitative trait genes (QTG) and nucleotides (QTN) in a QTL on chr13 associated with variation in basal glucose levels and in a QTL on chr6 associated with variation in tibia length.ConclusionsWe show how integrating genomic sequence with QTL reduces the QTL search space and helps researchers prioritize candidate genes and nucleotides for experimental follow-up. Additionally, given the LG/J and SM/J phylogenetic context among inbred strains, these data contribute important information to the genomic landscape of the laboratory mouse.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1592-3) contains supplementary material, which is available to authorized users.

Linkage Maps of a Mediterranean × Continental Tall Fescue Population and their Comparative Analysis with Other Poaceae Species.

Temperate grasses belonging to the Festuca-Lolium complex are important throughout the world in pasture and grassland agriculture. Tall fescue (Festuca arundinacea Schreb.) is the predominant species in the United States, covering approximately 15 million ha. Tall fescue has distinctive morphotypes, two of which are Continental (summer active) and Mediterranean (summer semidormant). This is the first report of a linkage map created for Mediterranean tall fescue, while updating the Continental map with additional simple sequence repeat and sequence-tagged site markers. Additionally, this is the first time that diversity arrays technology (DArT) markers were used in the construction of a tall fescue map. The male parent (Continental), R43-64, map consisted of 594 markers arranged in 22 linkage groups (LGs) and covered a total of 1577 cM. The female parent (Mediterranean), 103-2, map was shorter (1258 cM) and consisted of only 208 markers arranged in 29 LGs. Marker densities for R43-64 and 103-2 were 2.65 and 6.08 cM per marker, respectively. When compared with the other Poaceae species, meadow fescue (F. pratensis Huds.), annual ryegrass (L. multiflorum Lam.), perennial ryegrass (L. perenne L.), Brachypodium distachyon (L.) Beauv., and barley (Hordeum vulgare L.), a total of 171 and 98 orthologous or homologous sequences, identified by DArT analysis, were identified in R43-64 and 103-2, respectively. By using genomic in situ hybridization, we aimed to identify potential progenitors of both morphotypes. However, no clear conclusion on genomic constitution was reached. These maps will aid in the search for quantitative trait loci of various traits as well as help define and distinguish genetic differences between the two morphotypes.

Mapping epistatic quantitative trait loci.

BackgroundHow to map quantitative trait loci (QTL) with epistasis efficiently and reliably has been a persistent problem for QTL mapping analysis. There are a number of difficulties for studying epistatic QTL. Linkage can impose a significant challenge for finding epistatic QTL reliably. If multiple QTL are in linkage and have interactions, searching for QTL can become a very delicate issue. A commonly used strategy that performs a two-dimensional genome scan to search for a pair of QTL with epistasis can suffer from low statistical power and also may lead to false identification due to complex linkage disequilibrium and interaction patterns.ResultsTo tackle the problem of complex interaction of multiple QTL with linkage, we developed a three-stage search strategy. In the first stage, main effect QTL are searched and mapped. In the second stage, epistatic QTL that interact significantly with other identified QTL are searched. In the third stage, new epistatic QTL are searched in pairs. This strategy is based on the consideration that most genetic variance is due to the main effects of QTL. Thus by first mapping those main-effect QTL, the statistical power for the second and third stages of analysis for mapping epistatic QTL can be maximized. The search for main effect QTL is robust and does not bias the search for epistatic QTL due to a genetic property associated with the orthogonal genetic model that the additive and additive by additive variances are independent despite of linkage. The model search criterion is empirically and dynamically evaluated by using a score-statistic based resampling procedure. We demonstrate through simulations that the method has good power and low false positive in the identification of QTL and epistasis.ConclusionThis method provides an effective and powerful solution to map multiple QTL with complex epistatic pattern. The method has been implemented in the user-friendly computer software Windows QTL Cartographer. This will greatly facilitate the application of the method for QTL mapping data analysis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-014-0112-9) contains supplementary material, which is available to authorized users.

A genome-wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschl's gyrus.

Heschl's gyrus (HG) is a core region of the auditory cortex whose morphology is highly variable across individuals. This variability has been linked to sound perception ability in both speech and music domains. Previous studies show that variations in morphological features of HG, such as cortical surface area and thickness, are heritable. To identify genetic variants that affect HG morphology, we conducted a genome-wide association scan (GWAS) meta-analysis in 3054 healthy individuals using HG surface area and thickness as quantitative traits. None of the single nucleotide polymorphisms (SNPs) showed association P values that would survive correction for multiple testing over the genome. The most significant association was found between right HG area and SNP rs72932726 close to gene DCBLD2 (3q12.1; P=2.77 × 10(-7) ). This SNP was also associated with other regions involved in speech processing. The SNP rs333332 within gene KALRN (3q21.2; P=2.27 × 10(-6) ) and rs143000161 near gene COBLL1 (2q24.3; P=2.40 × 10(-6) ) were associated with the area and thickness of left HG, respectively. Both genes are involved in the development of the nervous system. The SNP rs7062395 close to the X-linked deafness gene POU3F4 was associated with right HG thickness (Xq21.1; P=2.38 × 10(-6) ). This is the first molecular genetic analysis of variability in HG morphology.